Of the more than 65 different human papillomavirus types (HPVs) about 20 are associated with lesions of the anogenital tract. The anogenital HPVs can be further subdivided into two groups: the "low risk" HPVs (e.g.) HPV-6 and HPV-ll) which are associated with benign lesions such as condyloma acuminata and the "high risk" HPVs (e.g., HPV-16 and HPV-18) which are associated with cervical carcinomas. The E7 gene of the "high risk" HPVs is consistently expressed in CINs as well as in cervical carcinomas and the derived cell lines. It encodes a 98 amino acid nuclear phosphoprotein that shares amino acid similarity with the adenovirus (Ad) EIA transforming proteins as well as the large tumor antigens (TAg) of the polyomaviruses. The biological properties that have been described for the HPV-16 E7 protein include transformation of established rodent fibroblast cell lines, cooperation with a ras oncogene to transform primary baby rat kidney cells, cooperation with the E6 oncoprotein to transform primary human epithelial cells, abrogation of the TGF beta mediated repression of c-myc expression and transactivation of the Ad E2 promoter. Biochemical studies have revealed that the HPV16 E7 protein can form a specific complex with the retinoblastoma tumor suppressor gene product pRB which is phosphorylated at serine residues by casein kinase II and exhibits anomalous migration properties on SDS polyacrylamide gels. The biological properties have been mapped to specific regions of the E7 protein and studies with chimeric HPV-6/HPV-16 E7 proteins have revealed differences in the biological and biochemical properties of E7 proteins derived from "high risk" HPVs and "low risk" HPVs.